Current guidelines recommend the use of mechanical thrombectomy (MT) plus IV thrombolysis (aka bridging therapy BT) for patients with anterior circulation large vessel occlusion (LVO) stroke. ...However, clinical equipoise exists in relation to the use of BT vs MT alone. Our objective is to compare the efficacy and safety of BT and MT for anterior circulation LVO.
A systematic search of biomedical literature databases was performed from inception to October 29, 2021, to identify prospective and retrospective studies comparing the rates for functional independence (modified Rankin Scale score 0-2) and mortality at 90 days, symptomatic intracranial hemorrhage (sICH), and successful recanalization rates for MT and BT. Effect size was represented by odds ratio (OR), and analysis was done with random-effects meta-analysis. Heterogeneity was assessed by
and Cochrane
statistics.
Overall, 41 studies with 14,885 patients were included. Mean ± SD age was 69 ± 11 years for BT and 70 ± 11 years for MT. All studies used alteplase as the thrombolytic agent. The BT group had 29% higher odds for functional independence (OR 1.29, 95% CI 1.16-1.44,
= 42%), 25% higher odds of successful reperfusion (OR 1.25, 95% CI 1.08-1.44,
= 42%), and 31% decrease in odds for mortality (OR 0.69, 95% CI 0.60-0.80,
= 47%) compared with MT. sICH prevalence was similar between groups (OR 1.10, 95% CI 0.95-1.28,
= 0%). Six of the studies were randomized controlled trials (RCTs) with intention-to-treat analysis done in patients presenting directly to MT-capable centers. When analysis was restricted to these 6 RCTs (n = 2,333), no differences were observed in functional independence (OR 1.08, 95% CI 0.91-1.27,
= 0%), sICH (OR 1.37, 95% CI 0.95-1.97,
= 0%), or mortality (OR 0.93, 95% CI 0.74-1.16,
= 0%) between groups. However, successful reperfusion favored the BT group (OR 1.35, 95% CI 1.06-1.73,
= 0%).
The odds for functional independence, successful reperfusion, and mortality for the entire dataset favored the use of BT over MT (medium heterogeneity and low quality of evidence). When analysis was restricted to RCTs, both treatments had similar functional and safety outcomes (no heterogeneity), but recanalization rates favored the BT group (no heterogeneity). Because these findings may differ in patients who present to non-MT-capable centers or with the use of other thrombolytic agents, further RCTs are needed.
Purpose of Review
Delayed cerebral ischemia (DCI) is common after subarachnoid hemorrhage (SAH) and represents a significant cause of poor functional outcome. DCI was mainly thought to be caused by ...cerebral vasospasm; however, recent clinical trials have been unable to confirm this hypothesis. Studies in humans and animal models have since supported the notion of a multifactorial pathophysiology of DCI. This review summarizes some of the main mechanisms under investigation including cerebral vascular dysregulation, microthrombosis, cortical spreading depolarizations, and neuroinflammation.
Recent Findings
Recent guidelines have differentiated between DCI and angiographic vasospasm and have highlighted roles of the microvasculature, coagulation and fibrinolytic systems, cortical spreading depressions, and the contribution of the immune system to DCI. Many therapeutic interventions are underway in both preclinical and clinical studies to target these novel mechanisms as well as studies connecting these mechanisms to one another.
Summary
Clinical trials to date have been largely unsuccessful at preventing or treating DCI after SAH. The only successful pharmacologic intervention is the calcium channel antagonist, nimodipine. Recent studies have provided evidence that cerebral vasospasm is not the sole contributor to DCI and that additional mechanisms may play equal if not more important roles.
•Intracerebral hemorrhage has a high morbidity and mortality rate.•Enhanced innate and peripheral immune inflammatory responses after intracerebral hemorrhage contributes to secondary brain ...injury.•The activity of the peripheral immune system can be estimated using the Systemic Immune-Inflammation Index.•Systemic Immune-Inflammation Index predicts poor outcome after intracerebral hemorrhage.
In experimental models, enhanced inflammation contributes to secondary brain injury in spontaneous intracerebral hemorrhage (ICH). Several inflammatory markers have investigated in humans with inconclusive results. Here, we report the relationship between Systemic Immune-Inflammation (SII) Index and outcome.
We reviewed the medical records of 239 supratentorial spontaneous ICH patients. Patients were dichotomized based on modified Rankin Scale (mRS) at discharge in good (mRS 0-3) and poor (mRS 4-6) outcome. Demographic, clinical, laboratory and imaging data at admission were compared for both groups. SII index was calculated as (Platelet counts x Absolute Neutrophil Counts (ANC)/Absolute Lymphocyte Counts (ALC))/1000. Logistic regression analyses were performed to determine the association between markers of inflammation (ANC, ALC, Platelets, SII index) and outcome adjusting for baseline differences.
Sixty-two percent of patients had poor outcome (median IQR age= 60 52-71 years). Patients with poor outcome had lower Glasgow coma scale, larger hematoma volumes, and higher incidence of diabetes and intraventricular extension (p<0.05 for each variable). In univariate analysis, ANC and SII index were independently associated with poor outcome (p<0.05). In multivariate analysis, only SII index remained significantly associated with poor outcome (OR=1.34, 95% CI=1.04-1.72, p=0.02). ROC analysis showed that adjusted SII index is a good discriminator for poor outcome (AUC=0.89, 95% CI=0.84–0.93; P <0.0001), with the best cut-off value being 0.73 (Sensitivity 95%, Specificity 71%).
In patients with supratentorial spontaneous ICH early SII index is an independent predictor of poor outcome at time of hospital discharge.
Aneurysmal subarachnoid hemorrhage has a high mortality rate and, for those who survive this devastating injury, can lead to lifelong impairment. Clinical trials have demonstrated that cerebral ...vasospasm of larger extraparenchymal vessels is not the sole contributor to neurological outcome. Recently, the focus of intense investigation has turned to mechanisms of early brain injury that may play a larger role in outcome, including neuroinflammation and microvascular dysfunction. Extravasated blood after aneurysm rupture results in a robust inflammatory response characterized by activation of microglia, upregulation of cellular adhesion molecules, recruitment of peripheral immune cells, as well as impaired neurovascular coupling, disruption of the blood–brain barrier, and imbalances in endogenous vasodilators and vasoconstrictors. Each of these phenomena is either directly or indirectly associated with neuronal death and brain injury. Here, we review recent studies investigating these various mechanisms in experimental models of subarachnoid hemorrhage with special emphasis on neuroinflammation and its effect on microvascular dysfunction. We discuss the various therapeutic targets that have risen from these mechanistic studies and suggest the utility of a multi-targeted approach to preventing delayed injury and improving outcome after subarachnoid hemorrhage.
This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people ...worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra. Furthermore, the interaction between inflammation and subsequent neurogenesis is not well understood but the close relationship between these two processes has garnered significant interest in the last decade or so. Current approved therapy for stroke involving pharmacological thrombolysis is limited in its efficacy and new treatment strategies need to be investigated. Research aimed at new therapies is largely about transplantation of neural stem cells and using endogenous progenitor cells to promote brain repair. By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) interacts with the low-density lipoprotein (LDL) receptor and, by enhancing its degradation, has a pivotal role in the regulation of cholesterol ...homeostasis. Two fully humanized monoclonal antibodies targeting PCSK9, evolocumab and alirocumab, are available for clinical use. PCSK9 inhibitors reduce LDL-C 30% more than ezetimibe and 60% more than placebo when added to statins. This reduction in LDL-C is accompanied by a decrease in the risk of major cardiovascular and cerebrovascular events. However, questions have been raised in relation to the cost-effectiveness of these medications. In this article, we review the clinical evidence on the use of PCSK9 inhibitors in lowering LDL-C and their effect on cerebrovascular health.
Bilirubin Encephalopathy Qian, Shuo; Kumar, Prateek; Testai, Fernando D.
Current neurology and neuroscience reports,
07/2022, Letnik:
22, Številka:
7
Journal Article
Recenzirano
Purpose of Review
Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy ...and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries.
Recent Findings
The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder.
Summary
Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.
Purpose of Review
Sickle cell anemia is a multiorgan disease with acute and chronic complications. Involvement of the central nervous system (CNS) is associated with increased mortality and ...morbidity. This review highlights the broad spectrum of neurological complications seen in patients with sickle cell disease.
Recent Findings
Increasing recognition of neurological complications has led to improved diagnostic and treatment options throughout the years. Neurologic complications in sickle cell disease include silent cerebral ischemia, ischemic/hemorrhagic stroke, moyamoya syndrome, posterior reversible encephalopathy syndrome, cerebral fat embolism, and cerebral venous sinus thrombosis. Treatment varies depending on the neurological complication.
Summary
Sickle cell disease is the most common hereditary anemia with increasing global disease burden. Early recognition and treatment is imperative.
Dual antiplatelet treatment (DAPT) with aspirin plus clopidogrel for a limited time is recommended after minor noncardioembolic stroke.
We performed a meta-analysis of all major studies that compared ...the efficacy and safety of DAPT versus monotherapy for the secondary prevention of recurrent stroke or transient ischemic attack. The primary outcomes were stroke and the composite of stroke, transient ischemic attack, acute coronary syndrome, and death from any cause. The safety outcome was major hemorrhage. Relative risk (RR) and 95% CIs were calculated. Heterogeneity was assessed by
and Cochrane Q statistics.
The analysis included 27 358 patients, the quality of evidence was moderate to low, and the heterogeneity for all the comparisons was low (
≤25%). Compared with monotherapy, DAPT reduced the risk of recurrent stroke (RR, 0.71 95% CI, 0.63-0.81) and composite outcome (RR, 0.76 95% CI, 0.69-0.83) but increased the risk of major bleeding (RR, 2.17 95% CI, 1.45-3.25). In the subgroup analysis, ≤30 days of DAPT increased the risk of hemorrhage relative to monotherapy (RR, 1.94 95% CI, 1.08-3.52). In the sensitivity analysis, the risk for hemorrhage with ≤30 days of DAPT after excluding the combination of aspirin plus ticagrelor was comparable to monotherapy (RR, 1.42 95% CI, 0.77-2.60). However, the risk for stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remain decreased compared with monotherapy.
DAPT decreases the risk of recurrent stroke and composite events compared with monotherapy. DAPT increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus ticagrelor.
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